N-alkylamides of D,L and L(-)-carnitine having antibacterial activity, process for their preparation and pharmaceutical and cosmetic compositions containing same

ABSTRACT

N-alkylamide of DL and L(-)-carnitine having general formula (I) ##STR1## wherein: x -   is OH -   or the anion of a pharmacologically acceptable acid (preferably Cl -` ), and 
     R is a straight C 10  -C 16  alkyl radical 
     are prepared via transamination by reacting DL or L(-)-carnitinamide halogenide with an amine of formula NH 2  R wherein R has the above-identified meaning in an acid environment (e.g. H 3  PO 4 ) in the presence of a high-boiling solvent (e.g. ethylene glycol). 
     N-alkylamides (I) are endowed with potent antibacterial activity and are suitable for preparing pharmaceutical and cosmetic compositions.

FIELD OF THE INVENTION

The present invention relates to novel N-alkylamides of D,L and L(-)-carnitine endowed with antibacterial activity, having general formula (I) ##STR2## wherein

X⁻ is OH⁻ or the anion of a pharmacologically acceptable acid, and

R is a straight C₁₀ -C₁₆ alkyl radical.

Preferably, X⁻ is Cl⁻.

The present invention also relates to a process for producing N-alkylamides of formula (I) and pharmaceutical and cosmetic compositions comprising an amount of at least one of the N-alkylamides (I) suitable for promoting an effective antibacterial action.

BACKGROUND OF THE INVENTION

Some carnitine N-alkylamildes are known already.

In Japanese patent 408435 filed Oct. 31, 1960 in the name of Takeda Chemical Industries, Ltd. carnitinamides structurally analogous to those of formula (I) are disclosed, wherein, however, the radical R is lower alkyl (methyl and ethyl). This Japanese patent discloses that such amides "promote the intestinal peristalsis and are useful as medicaments for intestinal disorders". These amides are prepared by condensing at room temperature a reactive carnitine derivative (an acid halogenide, ester or anhydride) with methylamine or ethylamine.

DETAILED DESCRIPTION

The N-alkylamides of D,L and L(-)-carnitine according to the present invention are unlike the amides of Japanese Patent 408435 prepared via a process which comprises the following two characterizing steps:

(a) reacting an alkylamine of formula NH₂ R wherein R is a straight C₁₀ -C₁₆ alkyl radical with a substantially equimolar amount of H₃ PO₄, at 120°-140° C., for 2-4 hours, in an atmosphere of an inert gas, in the presence of a high-boiling solvent; and

(b) adding to the reaction mixture a mixture of D,L or L(-)-carnitinamide chloride and alkylamine NH₂ R, at a molar ratio of about 1:1.1, the molar amount of D,L or L(-)-carnitinamide chloride being about twice as much the molar amount of H₃ PO₄ and keeping the resulting reaction mixture under stirring at about 110°-130° C. for about 34-38 hours in an atmosphere of inert gas.

After removal under vacuum of the high-boiling solvent, the residue comprising the N-alkylamide (I) is purified and the compound isolated according to known procedures.

The transamination of this process allows the direct conversion of the amide into the N-alkylamides (I) to be carried out. No intermediate steps are needed in order to convert the starting amide in one of those activated compounds (acid halogenides, esters or anhydrides) from which substituted amides are usually obtained (in this regard see the above mentioned Takeda patent). It is apparent that these intermediate steps would lower the yield remarkably and would increase the cost of the end product.

The following non-limiting example illustrates the preparation of one of the N-alkylamides (I) according to the process of this invention.

EXAMPLE Preparation of D,L-N-dodecylcarnitinamide chloride

A mixture of dodecylamine (25 m moles), ethylene glycol (20.0 grams) and 85% H (25 m moles) was reacted in a 100-ml round bottom flask, sealed with a rubber stopper, under stirring, at 130° C. for 3 hours under nitrogen.

A mixture of D,L-carnitinamide chloride (50 m moles) and dodecylamine (55 m moles) was then added to the reaction mixture.

The resulting mixture was kept under stirring at 120° C. for 36 hours under nitrogen. When ammonia development ceased, the reaction mixture was cooled and ethylene glycol caused to evaporate at 80° C. under 0.5 mm Hg.

After the residue was dissolved in 80 ml of chloroform, the resulting solution was chromatographed on a silica (50 g) containing column. The product was first eluted with chloroform (100 ml) and with 100 ml of a 9:1 chloroform: isopropanol mixture; then, the product was eluted with 300 ml of a 1:1 chloroform:methanol mixture. The product was recovered by evaporation from the solvent. By further crystallization from 100 ml of tetrahydrofurane and then 100 ml of a 1:1 chloroform:tetrahydrofurane mixture (twice repeated) the title compound was obtained ##EQU1##

Elementary analysis:

C=62.87%; H=11.50%; N=7.86%; Cl=10.25% O=7.52% .

Also the remaining N-alkylamides of D,L and L(-)-carnitine chloride encompassed in the general formula (I) were prepared by the same process. In the following table, the main chemico-physical characteristics of the compounds are listed.

    __________________________________________________________________________      ##STR3##                                                                                                           IR spectra                                Abbreviated                                                                               Molecular  Elementary Analysis                                                                           Freq.                                     R   name   weight                                                                               [α].sub.D.sup.25                                                              Theoretical (%)                                                                        Found (%)(*)                                                                          cm.sup.-1                                                                            Assignments                         __________________________________________________________________________     C.sub.10 H.sub.21                                                                  L(-) CA-10                                                                            336.92                                                                               -13.62°                                                                      C = 60.60                                                                              C = 60.72                                                                              950  OH                                      DL-CA-10     0°                                                                           H = 10.77                                                                              H = 10.54                                                                             1300  CN                                                        N = 8.31                                                                               N = 8.85                                                                              1470  CH.sub.2 and OH                                           Cl = 10.52                                                                             Cl = 10.00                                                                            1560  NH                                                        O = 9.50                                                                               O = 8.89                                                                              1650                                                                                  ##STR4##                           C.sub.11 H.sub.23                                                                  L(-) CA-11                                                                            350.97                                                                               -13.05°                                                                      C = 61.60                                                                              C = 61.93                                                                             2940  OH                                      DL-CA-11     0°                                                                           H = 10.91                                                                              H = 11.29                                                                             3300  OH                                                        N = 7.98                                                                               N = 8.05                                                                              The frequencies and the                                         Cl = 10.10                                                                             Cl = 9.80                                                                             corresponding assignments                                       O = 9.12                                                                               O = 8.84                                                                              can be regarded as identical              C.sub.12 H.sub.25                                                                  L(-) CA-12                                                                            364.97                                                                               -12.60°                                                                      C = 62.53                                                                              C = 62.87                                                                             for all the compounds                         DL-CA-12     0°                                                                           H = 11.05                                                                              H = 11.50                                                                             because the differences                                         N = 7.68                                                                               N = 7.86                                                                              between them are not                                            Cl = 9.71                                                                              Cl = 10.25                                                                            significant.                                                    O = 8.77                                                                               O = 7.52                                         C.sub.13 H.sub.27                                                                  L(-) CA-13                                                                            379.03                                                                               -12.23°                                                                      C = 63.34                                                                              C = 63.65                                            DL-CA-13     0°                                                                           H = 11.17                                                                              H = 10.81                                                              N = 7.39                                                                               N = 7.60                                                               Cl = 9.35                                                                              Cl =  9.02                                                             O = 8.44                                                                               O = 8.92                                         C.sub.14 H.sub.29                                                                  L(-) CA-14                                                                            393.03                                                                               -12.01°                                                                      C = 64.18                                                                              C = 64.94                                            DL-CA-14     0°                                                                           H = 11.28                                                                              H = 12.00                                                              N = 7.13                                                                               N = 7.19                                                               Cl = 9.02                                                                              Cl = 9.87                                                              O = 6.14                                                                               O = 6.00                                         C.sub.15 H.sub.31                                                                  L(-) CA-15                                                                            407.08                                                                               -11.62°                                                                      C = 64.91                                                                              C = 64.99                                            DL-CA-15     0°                                                                           H = 11.39                                                                              H = 10.92                                                              N = 6.88                                                                               N = 6.89                                                               Cl = 8.71                                                                              Cl = 8.69                                                              O = 7.86                                                                               O = 8.51                                         C.sub.16 H.sub.33                                                                  L(-) CA-16                                                                            421.08                                                                               -11.08                                                                              C = 65.61                                                                              C = 64.98                                            DL-CA-16     0°                                                                           H = 11.49                                                                              H = 11.87                                                              N = 6.65                                                                               N = 6.64                                                               Cl =  8.42                                                                             Cl = 8.97                                                              O = 7.60                                                                               O = 7.54                                         __________________________________________________________________________      (*) For both L(-) and DL form the "found" values are substantially             identical                                                                

TOXICOLOGICAL TESTS 1. Acute toxicity

(1.1) Acute toxicity via the oral route in mice

It was evaluated in albino Swiss mice weighing 20-25 g which had been kept fasting 12 hours before administration.

The compounds dissolved in distilled water were administrated to the animals by gavage.

The animals were divided in groups of 6 animals each and treated with solutions of diminishing concentrations, each concentration being one half of the preceding concentration.

The mice were checked for 7 days following administration in order to verify their possible death or any behavioural alteration.

LD₅₀ was evaluated by the Carrol Weil method (Biometrics, Sept. 1952, pages 249-255, "Calculation of median-effective dose").

The results thus obtained are illustrated in table 1 and 1A.

                  TABLE 1                                                          ______________________________________                                         Acute Toxicity via the oral route in mice                                      DL-CA-10      DL-CA-12  DL-CA-14   DL-CA-16                                    ______________________________________                                         LD.sub.50                                                                              791       1512      1125     1995                                      (mg/kg)                                                                        Dose                                                                           (mg/kg)                                                                        4000    --        6/6       6/6      6/6                                       2000    6/6       5/6       6/6      3/6                                       1000    3/6       0/6       2/6      0/6                                        500    0/6       0/6       0/6      0/6                                        250    0/6       --        --       --                                        ______________________________________                                    

                  TABLE 1A                                                         ______________________________________                                         Acute Toxicity via the oral route in mice                                      L(-)-CA-10    L(-)-CA-12                                                                               L(-)-CA-14 L(-)-CA-16                                  ______________________________________                                         LD.sub.50                                                                              890       1256      1125     1995                                      (mg/kg)                                                                        Dose                                                                           (mg/kg)                                                                        4000    --        6/6       6/6      6/6                                       2000    6/6       6/6       6/6      2/6                                       1000    4/6       1/6       2/6      1/6                                        500    0/6       0/6       0/6      0/6                                        250    0/6       --        --       --                                        ______________________________________                                    

(1.2) Acute toxicity via the intravenous route in mice

It was evaluated in albino Swiss mice weighing 20-25 g.

The animals were injected the compounds dissolved in saline solution, in their caudal vein.

The animals were divided in groups of 6 animals each and treated with solutions of diminishing concentration, each concentration being one half of the preceding concentration. The mice were checked for 48 hours following administration.

LD₅₀ was evaluated by the Carrol Weil method.

The results are illustrated in table 2 and 2A.

                  TABLE 2                                                          ______________________________________                                         Acute Toxicity via the intravenous route in mice                               DL-CA-10      DL-CA-12  DL-CA-14   DL-CA-16                                    ______________________________________                                         LD.sub.50                                                                              28.28     25.2      48.72    63.33                                     (mg/kg)                                                                        Dose                                                                           (mg/kg)                                                                        160     --        --        6/6      6/6                                       80      6/6       6/6       6/6      6/6                                       40      5/6       6/6       3/6      2/6                                       20      1/6       1/6       0/6      0/6                                       10      0/6       0/6       --       --                                        ______________________________________                                    

                  TABLE 2A                                                         ______________________________________                                         Acute Toxicity via the intravenous route in mice                               L(-)-CA-10    L(-)-CA-12                                                                               L(-)-CA-14 L(-)-CA-16                                  ______________________________________                                         LD.sub.50                                                                              28.28     25.2      63.33    56.42                                     (mg/kg)                                                                        Dose                                                                           (mg/kg)                                                                        160     --        --        6/6      6/6                                       80      6/6       6/6       6/6      6/6                                       40      5/6       6/6       2/6      0/6                                       20      1/6       1/6       0/6      0/6                                       10      0/6       0/6       --       --                                        ______________________________________                                    

(1.3) Assessment of the irritating activity on the rabbit eye

The Federal Register test (vol. 38, 1973) modified as hereinbelow indicated was used.

Six New Zealand albino rabbits, weighing 1.5-2 kgs, were used for each test substance. Throughout the test the animals were caged so as to exclude possible extraneous materials that may produce eye irritation.

0.1 ml of a 1% solution of the test compounds was instilled with a dropper into the conjunctival sac of the rabbit right eye (the contralateral eye remained untreated and served as a control), whereupon the animals were caged again.

The treated eyes of all the animals were examined, in comparison with the control eye, 24, 48 and, if necessary, 72 hours following treatment.

The irritating activity was rated based on the scoring scale outlined in table 3.

The results are illustrated in table 4 and 4A.

                  TABLE 3                                                          ______________________________________                                         Assessment of irritating activity on rabbit eyes                               ______________________________________                                         Conjunctivae                                                                   (a)   Conjestion                                                                     Vessels normal            0                                                    Vessels slightly injected 1                                                    Diffuse redness, vessels definetly injected                                                              2                                                    not easily discernible                                                         Diffuse, beefy red        3                                              (b)   Chemosis                                                                       No oedema                 0                                                    Slight oedema             1                                                    Severe oedema with eversion of lids                                                                      2                                                    Severe oedema with lids about half closed                                                                3                                                    Severe oedema with lids more than half closed                                                            4                                              Cornea                                                                         No alteration or opacity    0                                                  Scattered or confluent areas of opacity;                                                                   1                                                  details of iris visible                                                        Easily discernible translucent areas; details                                                              2                                                  of iris slightly obscured                                                      Nacreous area; no details of iris visible;                                                                 3                                                  contours of pupil barely discernible                                           Complete corneal opacity; iris not discernible                                                             4                                                  Iris                                                                           Normal                      0                                                  Markedly deepened folds, more numerous than                                                                1                                                  normal; congestion, swelling, moderate circum-                                 corneal injection; iris still reacting to light                                No reaction to light; haemorrhage; gross                                                                   2                                                  destruction                                                                    ______________________________________                                    

                  TABLE 4                                                          ______________________________________                                         Assessment of irritation activity on rabbit eyes                                        DL-CA-10  DL-CA-12  DL-CA-14                                                                               DL-CA-16                                           irritation                                                                               irritation                                                                               irritation                                                                             irritation                                RABBIT No.                                                                              score     score     score   score                                     ______________________________________                                         1        2         2         4       2                                         2        2         4         4       4                                         3        0         2         0       4                                         4        0         2         0       2                                         5        2         2         2       6                                         6        2         2         2       2                                         Average  1.3       2.3       2.0     3.3                                       score                                                                          ______________________________________                                    

                  TABLE 4A                                                         ______________________________________                                         Assessment of irritaiton activity on rabbit eyes                                        L(-)-CA-10                                                                               L(-)-CA-12                                                                               L(-)-CA-14                                                                             L(-)-CA-16                                         irritation                                                                               irritation                                                                               irritation                                                                             irritation                                RABBIT No.                                                                              score     score     score   score                                     ______________________________________                                         1        2         2         2       6                                         2        0         2         4       4                                         3        2         4         0       0                                         4        2         0         0       2                                         5        2         2         2       4                                         6        0         4         2       2                                         Average  1.3       2.3       1.5     3                                         score                                                                          ______________________________________                                    

(1.4) Assessment of the cutaneous irritation activity in rabbits

Irritation to the skin was evaluated by the method illustrated in Federal Register (vol. 38, No. 187, page 27019, 1973) on albino rabbits weighing about 2 kgs.

Two days before the test was commenced, the back of the rabbits was clipped free of hair with an electric shearing machine, taking care not to bring about irritations and abrasions.

At test beginning, a zone of the skin was abraded by a sterile syringe needle.

Both on the intact and abraded skin an AL-test patch soaked in a 20% solution of the test compound was secured in place.

Similar patches (controls) soaked in the same volume of saline solution were secured in place on the intact and abraded skin.

The AL-test patches were secured in place to the animals by antiallergic adhesive plasters

After 24 hours of exposures the patches were removed and the skin examined.

The reactions were evaluated at 24 and 72 hours on the basis of the table in Federal Register (see table 5). The results thus obtained are illustrated in table 6 and 6A.

                  TABLE 5                                                          ______________________________________                                         Assessment of the cutaneous irritating activity                                SKIN REACTIONS:                                                                ______________________________________                                         (1)   ERYTHEMA                                                                       No erythema                0                                                   Slight barely perceptible erythema                                                                        1                                                   Well-defined erythema      2                                                   Moderate to severe erythema                                                                               3                                                   Severe erythema (intense redness)                                                                         4                                                   to slight eschar formation                                               (2)   OEDEMA                                                                         No oedema                  0                                                   Slight, barely perceptible oedema                                                                         1                                                   Slight oedema (with well-defined edges)                                                                   2                                                   Moderate oedema (raised approximately 1 mm)                                                               3                                                   Severe oedema (raised more than 1 mm and                                                                  4                                                   extending beyond the exposure area)                                      ______________________________________                                    

The reaction value is the average of the values of six animals and is calculated by adding the values under 1) to the values under 2) for both intact and abraded skin. The resulting sum is divided by 24 and the result is termed "primary cutaneous irritation score".

The substance is regarded as:

non-irritating if the score is 0

mildly irritating if the score ranges between 0 and 2

averagely irritating if the score ranges between 2 and 5

severely irritating if the score ranges between 5 and 8

                                      TABLE 6                                      __________________________________________________________________________     Assessment of the cutaneous irritating activity                                __________________________________________________________________________              DL-CA-10 (*)              DL-CA-12 (**)                                        Erythema value after                                                                      Oedema value after                                                                            Erythema value after                                                                      Oedema value after               Rabbit                                                                             Skin 24 hours                                                                            72 hours                                                                             24 hours                                                                            72 hours                                                                            Total                                                                               24 hours                                                                            72 hours                                                                             24 hours                                                                            72 hours                                                                              Total                __________________________________________________________________________      1   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            2   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            3   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            4   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            5   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            6   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                           irritation score                                                                        0                         1                                           __________________________________________________________________________              DL-CA-14 (**)             DL-CA-16 (*)                                         Erythema value after                                                                      Oedema value after                                                                            Erythema value after                                                                      Oedema value after               Rabbit                                                                             Skin 24 hours                                                                            72 hours                                                                             24 hours                                                                            72 hours                                                                            Total                                                                               24 hours                                                                            72 hours                                                                             24 hours                                                                            72 hours                                                                              Total                __________________________________________________________________________      1   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                     2   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                     3   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                     4   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                     5   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0      0   0    0    0    0     0    0      0                     6   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                    irritation score                                                                        0                         0                                           __________________________________________________________________________      (*) Exposure period: 4 hours                                                   (**) Exposure period: 24 hours                                           

                                      TABLE 6A                                     __________________________________________________________________________     Assessment of the cutaneous irritating activity                                __________________________________________________________________________              L(-)-CA-10 (*)            L(-)-CA-12 (**)                                      Erythema value after                                                                      Oedema value after                                                                            Erythema value after                                                                      Oedema value after               Rabbit                                                                             Skin 24 hours                                                                            72 hours                                                                             24 hours                                                                            72 hours                                                                            Total                                                                               24 hours                                                                            72 hours                                                                             24 hours                                                                            72 hours                                                                              Total                __________________________________________________________________________      1   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            2   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            3   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            4   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            5   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                            6   intact                                                                              0    0     0    0    0    0    0     2    0                                                                                    4                        abraded                                                                             0    0     0    0    0    0    0     2    0                           irritation score                                                                        0                         1                                           __________________________________________________________________________              L(-)-CA-14 (**)           L(-)-CA-16 (*)                                       Erythema value after                                                                      Oedema value after                                                                            Erythema value after                                                                      Oedema value after               Rabbit                                                                             Skin 24 hours                                                                            72 hours                                                                             24 hours                                                                            72 hours                                                                            Total                                                                               24 hours                                                                            72 hours                                                                             24 hours                                                                            72 hours                                                                              Total                __________________________________________________________________________      1   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                     2   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                     3   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                     4   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                     5   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0      0   0    0    0    0     0    0      0                     6   intact                                                                              0    0     0    0    0    0    0     0    0      0                       abraded                                                                             0    0     0    0    0    0    0     0    0      0                    irritation score                                                                        0                         0                                           __________________________________________________________________________      (*) Exposure period: 4 hours                                                   (**) Exposure period: 24 hours                                           

ANTIBACTERIAL ACTIVITY

in vitro

1.1 Determination of antibacterial activity on Petri plates

The test was carried out on sterile Petri plates (14 cm of diameter), by inoculating the strains listed at point A in suitable culture media by the Kirby-Bauer method. A)

1 - Bacillus subtilis ATCC 6633 on Muller Hinton agar

2 - Escherichia coli ATCC 25922 on Muller Hinton agar

3 - Staphylococcus aureus ATCC 6538 on Muller Hinton agar

4 - Mucor mucedo ATCC 7941 on Sabouraud maltose agar

5 - Candida albicans ATCC 2091 on Sabouraud maltose agar

The antibacterial activity of the compounds was evaluated by means of a well on the solidified medium. The results are shown in table 7 and 7A.

                  TABLE 7                                                          ______________________________________                                         Antibacterial Activity (diameter in mm)                                        Con-                                       Mucor                               centra-                                                                              (DL)               Staph.                                                                               Bac.  Cand. mucedo                              tion  Compound   E. coli aureus                                                                               subtilis                                                                             albic.                                                                               (*)                                 ______________________________________                                         0,1%  C10        10.7    10.8  14.0  12.7  +-                                        C12        19.1    16.9  18.0  17.3  ++                                        C14        10.6    10.3  10.9  13.4  +-                                        C16        10.4    10.6   9.9  13.5  +                                    1%   C10        14.1    14.6  27.1  24.0  ++                                        C12        28.6    19.8  23.0  24.8   +++                                      C14        12.7    13.0  12.4  16.8  +-                                        C16        11.0    12.4  11.0  14.7  +                                   10%   C12        30.6    21.8  27.0  25.0   +++                                      C14        15.4    18.1  17.0  17.9  +-                                        C16        11.4    16.1  14.6  16.0  +                                         DL-carnitina-                                                                             --      --    --    --    --                                        mide-chloride                                                            ______________________________________                                         (*) +- =                                                                               10.0 to 12.0 mm in diameter                                            + =     12.0 to 19.0 mm in diameter                                            ++ =    19.0 to 29.0 mm in diameter                                            +++ =   29.0 to 35.0 mm in diameter                                       

                  TABLE 7A                                                         ______________________________________                                         Antibacterial Activity (diameter in mm)                                        Con-                                       Mucor                               centra-                                                                              (DL)               Staph.                                                                               Bac.  Cand. mucedo                              tion  Compound   E. coli aureus                                                                               subtilis                                                                             albic.                                                                               (*)                                 ______________________________________                                         0,1%  C10        10.8    11.5  13.0  12.3  +-                                        C12        20.7    15.6  19.0  18.2  ++                                        C14        10.6    11.4  10.1  13.8  +-                                        C16        10.9    10.6   9.6  12.0  +                                    1%   C10        14.8    15.3  24.1  21.0  ++                                        C12        28.8    18.8  26.0  23.9   +++                                      C14        11.0    14.1  12.9  16.1  +                                         C16        10.6    13.2  11.5  13.0  +                                   10%   C12        30.6    20.5  27.9  24.8   +++                                      C14        16.3    19.6  18.1  19.3  +                                         C16        11.5    15.9  13.6  16.4  +                                         DL-carnitina-                                                                             --      --    --    --    --                                        mide-chloride                                                            ______________________________________                                         (*) +- =                                                                               10.0 to 12.0 mm in diameter                                            + =     12.0 to 19.0 mm in diameter                                            ++ =    19.0 to 29.0 mm in diameter                                            +++ =   29.0 to 35.0 mm in diameter                                       

in vitro

2.1 Determination of Minimum Inhibiting Concentration (MIC)

The test was carried out on sterile Petri dishes (10 cm of diameter) loaded with 10 ml of medium and anti-bacterial substance at given concentration, mixed at 9:1 ratio.

The medium used was

(1) Muller Hinton agar for bacteria, and

(2) Sabouraud Dextrose agar for fungi

The solidified plates were then inoculated at the surface thereof with a multi-point inoculator equipped with 48 rods, each of which had been coated with a suspension of the tested microorganism. The suspensions were prepared with the Kirby-Bauer method (Bauer, Kirby, Sherris, Turck 1966, Am. J. Clin. Pathol. 45:49-496) modified according to D'Amato-Hochstein (D'Amato-Hochstein, 1982, J. Clin. Microb. 15 (2) 282-285).

The inoculated plates were incubated at 35° C. (culture medium (1)) and 25° C. (culture medium (2)) respectively.

Reading was carried out after 15-18 hours for bacteria and after 24-30 hours for fungi.

MIC values thus obtained are shown in table 8 and 8A.

                                      TABLE 8                                      __________________________________________________________________________     Minimum Inhibiting Concentration (mcg)                                         Method: Petri dishes with solid culture medium                                                   DL-CA-10                                                                             DL-CA-12                                                                             DL-CA-14                                                                             DL-CA-16                                   __________________________________________________________________________     Staphylococcus aureus                                                                      10547 62    15    15    15                                          "          8530  62    31    15    15                                          "          6538P 31    62    250   >500                                        "          80R   62    15    15    15                                          "          58R   62    62    31    31                                         Enterococcus                                                                               1 Renz.                                                                              62    7     <7    <7                                          "          2 Renz.                                                                              62    7     <7    <7                                         Strept. faecalis lactis R                                                                  8043  62    <7    <15   <7                                          "          66/48 62    7     <7    <7                                         Strept. faecium                                                                            UM    31    <7    <7    <7                                         Sarcina lutea                                                                              9341  250   62    62    15                                         Bacillus subtilis                                                                          6633  62    15    15    31                                         Pseudomonas aeruginosa                                                                     3E    >500  250   >500  >500                                        "          50F   >500  250   >500  >500                                        "          12F   >500  125   >500  >500                                       Salmonella typhi                                                                           SK    125   62    250   >500                                       Salmonella typhi                                                                           6539  62    31    15    31                                         Enterobacter cloacae                                                                       P99 β -Latt.                                                                    250   31    125   >500                                       Shigella somnei                                                                            SK    125   62    200   >500                                       Escherichia coli                                                                           4     125   62    250   >500                                        "          828   500   125   >500  >500                                        "          92F   250   62    250   >500                                        "          66/46 125   62    >500  >500                                        "          R57B  250   125   >500  500                                        Klebsiella pneumoniae                                                                      IB 1 (pat.)                                                                          500   31    250   500                                        Candida albicans                                                                           A 215 250   62    15    125                                         "          i6    250   62    15    62                                          "          ISS 562                                                                              250   62    15    62                                         Candida tropicalis                                                                         ISS 5705                                                                             250   <7    31    7                                          Mucor mucedo                                                                               7941  250   15    15    62                                         Aspergillus niger                                                                          9642  500   15    15    15                                         __________________________________________________________________________

                                      TABLE 8A                                     __________________________________________________________________________     Minimum Inhibiting Concentration (mcg)                                         Method: Petri dishes with solid culture medium                                                   L(-)-CA-10                                                                           L(-)-CA-12                                                                           L(-)-CA-14                                                                           L(-)-CA-16                                 __________________________________________________________________________     Staphylococcus aureus                                                                      10547 31    15    15    15                                          "          8530  31    31    62    15                                          "          6538P 62    62    250   >500                                        "          80R   62    15    15    15                                          "          58R   62    15    15    15                                         Enterococcus                                                                               1 Renz.                                                                              62    7     15    <7                                          "          2 Renz.                                                                              62    7     <7    <7                                         Strept. faecalis lactis R                                                                  8043  62    <7    <7    15                                          "          66/48 62    7     <7    <7                                         Strept. faecium                                                                            UM    31    <7    <7    <7                                         Sarcina lutea                                                                              9341  125   62    62    31                                         Bacillus subtilis                                                                          6633  125   15    15    31                                         Pseudomonas aeruginosa                                                                     3E    >500  250   >500  >500                                        "          50F   >500  62    >500  >500                                        "          12F   >500  125   >500  >500                                       Salmonella typhi                                                                           SK    125   62    250   250                                        Salmonella typhi                                                                           6539  62    31    15    31                                         Enterobacter cloacae                                                                       P99 β-Latt.                                                                     125   62    125   >500                                       Shigella somnei                                                                            SK    125   62    200   >500                                       Escherichia coli                                                                           4     125   62    250   >500                                        "          828   250   125   >500  >500                                        "          92F   500   62    500   >500                                        "          66/46 125   125   >500  >500                                        "          R57B  500   250   >500  >500                                       Klebsiella pneumoniae                                                                      IB 1 (pat.)                                                                          500   62    250   >500                                       Candida albicans                                                                           A 215 250   62    15    125                                         "          i6    250   62    15    62                                          "          ISS 562                                                                              250   31    31    31                                         Candida tropicalis                                                                         ISS 5705                                                                             250   <7    31    15                                         Mucor mucedo                                                                               7941  250   15    15    62                                         Aspergillus niger                                                                          9642  500   15    31    15                                         __________________________________________________________________________

ANTIDANDRUFF ACTIVITY

in vitro

3. DL and L(-) activity on Pityrosporum ovalis ATCC 12078

The test was carried out on sterile Petri plates having 10 cm of diameter filled with 10 ml of medium inoculated with the tested microorganism.

Sabouraud maltose agar+1% Tween 80 was used as culture medium.

The Kirby-Bauer method modified according to D'Amato-Hochstein was used.

The plates after inoculation by means of wells on the agar-containing medium were incubated at 35° C. for 48 hours.

The diameter of the growth inhibition zone was 20.3 mm for the 1% DL solution and 20.5 mm for the 1% L(-) solution and 9.91 mm for the 0.1% DL solution and 10.2 for the 0.1% L(-) solution.

3.2 Minimum inhibiting concentration of DL and L(-) CA-12 on Pityrosporum ovalis ATCC 12078

The test was carried out following the method outlined at point 2.1, except that the medium was modified by the addition of 1% Tween 80. The resulting MIC was 50 mcg for both DL and L(-).

The compounds of the invention are suitable for being compounded into pharmaceutical, cosmetic and over-the-counter (OTC) compositions, such as mouthwashes, external disinfectants, deodorants, shaving creams and the like. It was found that, generally, the optimum concentration of N-alkylamides of formula (I) in the compositions is 0.1-0.3% by weight for a preservative action and 0.3-1% by weight for a disinfectant action.

Some compositions according to the invention are hereinbelow indicated.

    ______________________________________                                         Alcoholic deodorant                                                            Ethanol               42 g                                                     Perfume               0.1 g                                                    DL or L(-) CA-12      0.1 g                                                    Propylene glycol      3 g                                                      Softigen 767          0.5 g                                                    Deionized water       balance to 100 g                                         Alcohol-free deodorant                                                         Ethanol               3 g                                                      Solulan C 24          1 g                                                      Perfume               0.1 g                                                    Propylene glycol      3 g                                                      DL or L(-) CA-12      0.1 g                                                    Lanidrol (lanolin alcohol)                                                                           0.5 g                                                    Deionized water       balance to 100 g                                         Shaving cream                                                                  Esso wax 5250         6 g                                                      Marcol 52             6.5 g                                                    Laurex CS             10 g                                                     Tween 60              3 g                                                      Silicone oil AK 350   1 g                                                      Butylhydroxyanisole   0.05 g                                                   Steinamid P256        1.7 g                                                    DL or L(-) CA-12      0.15 g                                                   EDTA                  0.2 g                                                    (ethylenediaminetetraacetic acid)                                              Propylene glycol      3 g                                                      Empigen BT            5 g                                                      Polimer JR 400        0.1 g                                                    Perfume               0.35 g                                                   Deionized water       balance to 100 g                                         Liquid detergent                                                               Empilan 2574          1 g                                                      Tween 20              2.4 g                                                    Tween 80              1.5 g                                                    Empigen BT            40 g                                                     Zetesol 250           7.6 g                                                    Neo extrapon lemon    0.1 g                                                    Sigma antioxidant     0.1 g                                                    EDTA                  0.1 g                                                    DL or L(-) CA-12      0.15 g                                                   Solulan 16            0.6 g                                                    Phosphoric acid       0.12 g                                                   Coconut oil diethanolamide                                                                           3 g                                                      Deionized water       balance to 100 g                                         Chewing gum                                                                    Chlorofil             0.0027 g                                                 Sodium fluoride       0.0152 g                                                 DL or L(-) CA-12      0.667 g                                                  Micronized sorbitol   35.78 g                                                  Micronized mannitol   13.55 g                                                  Gum base              28.74 g                                                  Aroma                 0.282 g                                                  Menthol               0.406 g                                                  70% sorbitol solution 17.35 g                                                  ______________________________________                                     

What is claimed is:
 1. N-alkylamides of DL and L(-)-carnitine having general formula (I) ##STR5## wherein: X⁻ is OH⁻) or the anion of a pharmacologically acceptable acid, andR is a straight C₁₀ -C₁₆ alkyl radical.
 2. N-alkylamides of DL and L(-)-carnitine according to claim 1, wherein X⁻ is Cl⁻.
 3. A composition suitable for topical application having antibacterial activity which comprises an amount effective for exerting a disinfectant action of a first component comprising at least one of the N-alkylamides of DL and L(-)-carnitine of claim 1, and a second component comprising a carrier or diluent.
 4. The composition of claim 3 comprising about 0.3-1.0% by weight of one of the N-alkylamides of DL and L(-)-carnitine of claim
 1. 5. The composition of claim 3 wherein the second component is a carrier which is a pharmaceutically or cosmetically acceptable vehicle for the topical application of said composition.
 6. The composition of claim 5 wherein the pharmaceutically or cosmetically acceptable vehicle makes said composition suitable for topical application as a mouthwash, external disinfectant, deodorant, face cream, body cream or shaving cream. 